This invention relates to a method of in situ manufacture of live autogenous replacement body parts such as skeletal parts, e.g. joints. More particularly, the invention is concerned with matrix materials and methods for the manufacture of live autogenous replacement parts comprising plural different tissues.
Bony defects, whether from degenerative, traumatic or cancerous etiologies, pose a formidable challenge to the reconstructive surgeon Although many types of bone grafts and numerous biocompatible materials have been used clinically they all suffer from shortcomings or potential long term complications See, for example, Urist, "Bone Transplants and Implants" in Fundamental and Clinical Bone Physiology, Chapter 11, Lippincott, Philadelphia, Pa., 1980 pp. 331-368; Habal and Reddi, "An Update on Bone Grafting and Bone Substitutes in Reconstructive Surgery" in Advances in Plastic and Reconstructive Surgery, Year Book Medical Publishers, Chicago, Ill., 1987, pp. 147-209.
More difficult still is the reconstruction or repair of skeletal parts comprising multiple different structural tissues. For example, joint reconstruction requires repair of both the bony defect and the articular cartilage. To date there are no satisfactory clinical means for readily repairing both cartilage and bony defects within a joint, and which result in viable, fully functional joints. Replacement with prosthetic joints is currently the only option for serious degeneration of joint function. It is anticipated that a means for functional reconstruction of joint complexes will have a profound effect on the management of degenerative joint disease and alloplastic joint replacement surgery.
True osteogenic factors capable of inducing the cascade of events that result in endochondral bone formation now have been identified, isolated and cloned. These proteins, when implanted in a mammal, typically in association with a matrix that allows the attachment, proliferation and differentiation of migratory progenitor cells, are capable of inducing recruitment of progenitor cells, stimulating their proliferation and inducing differentiation into chondrocytes and osteoblasts, and inducing differentiation of cartilage, vascular invasion, bone formation, remodeling, and finally marrow differention. More recently, these factors have been shown capable of generation of tissue of mesenchynal origin more generally, including liver and nerve tissue.
A particularly useful osteogenic protein is human OP1 (Osteogenic Protein-1), described in U.S. Pat. No. 5,011,691, U.S. Pat. No. 5,266,683 the disclosures of which are incorporated by reference and Ozkaynak et al. (1990) EMBO J. 9: 2085-2093. Species homologs identified to date include mouse OP-1 (see U.S. Pat. No. 5,266,683) and the Xenopus homolog 60A, described in Wharton et al. (1991) PNAS 88:9214-9218). Other closely related proteins include OP2 (Ozkaynak (1992) J. Biol. Chem. 267:25220-25227 and U.S. Pat. No. 5,266,683), BMP5, and 6 (Celeste et al. (1991) PNAS 87:9843-9847) and Vgr-1 (Lyons et al. (1989). These disclosures disclose the sequences and chemical and physical characteristics of these proteins. U.S. Pat. Nos. 5,011,691 and 5,266,683 also provide detailed descriptions for formulating and assaying osteoinductive devices useful for inducing bone formation in mammals. Other related osteoinductive proteins include BMP 2, 3, 4 (Wozney et al. (1988) Science 242:1528-1534); BMP 9 (WO93/00432, published Jan. 7, 1993); DPP (Padgett et al. (1987) Nature 325:81-84, and Vg-1 (Weeks (1987, Cell 51:861-867).
It is an object of the instant invention to provide a matrix suitable for regenerating body parts comprising two or more functionally and structurally associated different replacement tissues in an animal. It is another object to provide devices and methods for the reconstruction of viable, functional body parts comprising plural tissues, e.g., organs such as liver or joints comprising new bone and articular/cartilage.